US5670172A - Pharmaceutical spheroid formulation - Google Patents

Pharmaceutical spheroid formulation Download PDF

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Publication number
US5670172A
US5670172A US08/426,065 US42606595A US5670172A US 5670172 A US5670172 A US 5670172A US 42606595 A US42606595 A US 42606595A US 5670172 A US5670172 A US 5670172A
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US
United States
Prior art keywords
controlled release
weight
diltiazem
amount
composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US08/426,065
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English (en)
Inventor
Ian Richard Buxton
Helen Critchley
Stewart Thomas Leslie
Derek Allan Prater
Ronald Brown Miller
Sandra Therese Antoinette Malkowska
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Euro Celtique SA
Original Assignee
Euro Celtique SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB919117361A external-priority patent/GB9117361D0/en
Priority claimed from GB919122967A external-priority patent/GB9122967D0/en
Application filed by Euro Celtique SA filed Critical Euro Celtique SA
Priority to US08/426,065 priority Critical patent/US5670172A/en
Application granted granted Critical
Publication of US5670172A publication Critical patent/US5670172A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/501Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5015Organic compounds, e.g. fats, sugars
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005Wall or coating material
    • A61K9/5021Organic macromolecular compounds
    • A61K9/5036Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/08Vasodilators for multiple indications
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives

Definitions

  • the present invention relates to a controlled release preparation and to a process for its preparation.
  • a controlled release preparation containing diltiazem.
  • Diltiazem is a calcium antagonist which has been shown to be useful in treating chronic heart disease such as hypertension and angina.
  • the present invention is related to a controlled release composition
  • a controlled release composition comprising spheroid cores comprising diltiazem or a pharmaceutically acceptable salt thereof in an amount effective to render a therapeutic effect, and optionally a spheronizing agent, the cores being coated with a controlled release material in an amount effective to provide a controlled release of diltiazem when said composition is exposed to aqueous solutions.
  • the controlled release layer is provided in an amount suitable to provide a once daily dosage regimen.
  • the present invention is also related to a process for preparing a controlled release oral dosage preparation of diltiazem, comprising (a) granulating a mixture comprising diltiazem or a pharmaceutically acceptable salt thereof with water and optionally a spheronizing agent; (b) extruding the granulated mixture to obtain an extrudate; (c) spheronizing the extrudate until spheroid cores are formed; (d) drying the spheroid cores; and (e) coating the spheroid cores with a controlled release material. Thereafter, the coated spheroid cores are filled into capsules or sachets or compressed into tablets in an amount effective to provide a therapeutic dosage of diltiazem when ingested orally by a patient.
  • the resultant controlled release formulation of diltiazem is a one-a-day dosage.
  • Diltiazem is a calcium antagonist (calcium channel blocker) commonly available as the hydrochloride salt and having the chemical name 1,5-Benzothiazepin-4(5H)one,3-(acetyloxy)-5- 2-(dimethylamino)-ethyl!-2,3-dihydro-2-(4-methoxyphenyl)-, monohydrochloride, (+) -cis-.
  • Suitable pharmaceutically acceptable salts of diltiazem for use according to the present invention include pharmaceutically acceptable acid addition salts.
  • the hydrochloride salt is particularly preferred.
  • a controlled release pharmaceutical composition according to the present invention is one that achieves slow release of a drug over an extended period of time and extends the duration of drug action over that achieved by conventional delivery.
  • spheroid is conventional in the pharmaceutical art and means a spherical granule having a diameter of between 0.1 mm and 2.5 mm, especially between 0.5 mm and 2 mm.
  • the spheroid cores for use according to the present invention preferably contain from about 40% to about 98%, more preferably from about 60% to about 85%, and most preferably from about 70% to about 85% by weight of diltiazem or its pharmaceutically acceptable salts.
  • the spheronizing agent may comprise any pharmaceutically acceptable material which may be spheronized together with the active ingredient to form spheroid cores.
  • a preferred spheronizing agent is microcrystalline cellulose.
  • the microcrystalline cellulose employed may be, for example, Avicel PH 101 or Avicel PH 102 (TMFMC Corporation).
  • the spheronizing agent when present, is present in an amount of from 1% to 60%, and preferably from 15% to 40%, by weight of the spheroid cores.
  • the spheroid cores may also contain other pharmaceutically acceptable excipients and diluents which facilitate spheronization such as pharmaceutically acceptable sugars (for example sucrose, dextrose, maltose or lactose) or pharmaceutically acceptable sugar alcohols (for example mannitol, xylitol or sorbitol). Colorants may also be included in the spheroid core.
  • pharmaceutically acceptable sugars for example sucrose, dextrose, maltose or lactose
  • pharmaceutically acceptable sugar alcohols for example mannitol, xylitol or sorbitol.
  • Colorants may also be included in the spheroid core.
  • the spheroid cores are coated with a material which permits release of the diltiazem at a controlled rate in an aqueous medium.
  • Suitable controlled release coating materials include those well known in the art such as water insoluble waxes and polymers such as polymethacrylates (for example, Eudragit polymersTM) or, preferably, water insoluble celluloses (for example, alkylcelluloses such as ethylcellulose).
  • the coating may also include water soluble polymers such as polyvinylpyrrolidone or, preferably, a water soluble cellulose such as hydroxypropylmethylcellulose and/or hydroxypropylcellulose. It will be appreciated that the ratio of water insoluble to water soluble material will depend on the release rate required and the solubility of the materials selected. The ratio of water soluble polymer to water insoluble polymer is preferably from about 1:20 to about 1:2.
  • the controlled release coating preferably includes one or more pharmaceutically acceptable plasticizers conventional in the art such as diethylphthalate, or, preferably, dibutyl sebacate; surfactants such as sorbitan trioleate, sorbitan monolaurate, or, preferably, polysorbate 80 (Tween 80TM); and tack-modifiers, such as talc, or, preferably, colloidal anhydrous silica.
  • plasticizers conventional in the art such as diethylphthalate, or, preferably, dibutyl sebacate
  • surfactants such as sorbitan trioleate, sorbitan monolaurate, or, preferably, polysorbate 80 (Tween 80TM)
  • tack-modifiers such as talc, or, preferably, colloidal anhydrous silica.
  • the amount of plasticizer, when present, will depend on the particular plasticizer selected. In general, the plasticizer is present in an amount from about 1% to about 25% by weight of the controlled release film coat.
  • the surfactant, when present, is suitably present in an amount from about 1% to about 25% by weight of the controlled release film coat.
  • the tack-modifier, when present, is also suitably present in an amount from about 1% to about 25% by weight of the controlled release film coat.
  • a preferred controlled release film coating in accordance with the present invention comprises from about 50% to about 95% ethylcellulose, from about 5% to about 15% colloidal anhydrous silica, from about 5% to about 15% dibutyl sebacate, and from about 5% to about 15% polysorbate 80 (Tween 80TM).
  • the controlled release film coating layer can be formed on the surface of the diltiazem-containing spheroid cores using conventional coating methods, for example fluidized bed or pan coating.
  • the coating materials may be applied as a solution or suspension. Suitable solvent systems include water, dichloromethane, ethanol, methanol, isopropyl alcohol and acetone mixtures thereof, and the like.
  • the coating solution or suspension preferably contains from about 2% to about 60%, and preferably from about 2% to about 20% by weight of coating materials.
  • the amount of the controlled release coating material applied onto the spheroid cores will depend on the desired release rate. Generally, the amount of the controlled release coating material in the formulation is in the range of from about 1% to about 25%, and preferably from about 2% to about 8%, by weight of the composition.
  • the controlled release composition according to the invention may be prepared by:
  • compositions according to the invention may be filled into capsules or sachets or compressed into tablets using conventional pharmaceutical techniques.
  • the composition according to the present invention may be orally administered once daily.
  • the dosage form contains from 120 mg to 300 mg to diltiazem or a pharmaceutically acceptable salt thereof, preferably diltiazem hydrochloride.
  • Example 1 diltiazem capsules were prepared in accordance with the present invention.
  • diltiazem hydrochloride and microcrystalline cellulose were blended using a high shear mixer. The mixture was wet granulated, and extruded to give an extrudate which was spheronized and dried in a fluid bed drier. The spheroids were sieved to give a particle size of 0.85 to 1.7 mm.
  • the diltiazem spheres had the composition set forth in Table 1 below:
  • the controlled release film coating ingredients ethylcellulose, colloidal anhydrous silica, dibutyl sebacate, and polysorbate 80, were dispersed in a dichloromethane/methanol solvent system.
  • the amounts of the above materials used to prepare the coating are set forth in Table 2 below:
  • the controlled release film coat was then applied to the diltiazem spheroid cores in a fluid bed coater.
  • the resulting film coated spheroids were sieved.
  • the coated spheroids were filled into gelatin capsule shells. Further information is provided in Table 3 below:

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Inorganic Chemistry (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Steroid Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Fertilizers (AREA)
  • Compounds Of Unknown Constitution (AREA)
US08/426,065 1991-08-12 1995-04-21 Pharmaceutical spheroid formulation Expired - Lifetime US5670172A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US08/426,065 US5670172A (en) 1991-08-12 1995-04-21 Pharmaceutical spheroid formulation

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
GB919117361A GB9117361D0 (en) 1991-08-12 1991-08-12 Oral dosage form
GB911761 1991-08-12
GB919122967A GB9122967D0 (en) 1991-10-29 1991-10-29 Pharmaceutical composition
GB9122967 1991-10-29
US92650192A 1992-08-05 1992-08-05
US08/426,065 US5670172A (en) 1991-08-12 1995-04-21 Pharmaceutical spheroid formulation

Related Parent Applications (1)

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US92650192A Continuation 1991-08-12 1992-08-05

Publications (1)

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US5670172A true US5670172A (en) 1997-09-23

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US08/666,636 Expired - Lifetime US5601845A (en) 1991-08-12 1996-06-18 Pharmaceutical spheroid formulation

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US08/666,636 Expired - Lifetime US5601845A (en) 1991-08-12 1996-06-18 Pharmaceutical spheroid formulation

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US (2) US5670172A (no)
EP (1) EP0527637B1 (no)
JP (1) JP3019235B2 (no)
KR (1) KR100221695B1 (no)
CN (1) CN1052398C (no)
AT (1) ATE165513T1 (no)
AU (1) AU651715B2 (no)
CA (1) CA2075356A1 (no)
DE (1) DE69225278D1 (no)
ES (1) ES2115643T3 (no)
FI (1) FI923582A (no)
IL (1) IL102778A (no)
NO (1) NO304406B1 (no)
PH (1) PH31288A (no)

Cited By (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6013284A (en) * 1993-03-02 2000-01-11 Biovector Therapeutics S.A. Synthetic particulate vectors and preparation process
US6033687A (en) * 1995-01-05 2000-03-07 F.H. Faulding & Co. Controlled absorption diltiazem pharmaceutical formulation
US6103261A (en) * 1993-07-01 2000-08-15 Purdue Pharma Lp Opioid formulations having extended controlled release
US6129933A (en) * 1991-12-24 2000-10-10 Purdue Pharma Lp Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US6399096B1 (en) 1995-09-22 2002-06-04 Euro-Celtique S.A. Pharmaceutical formulation
US6524620B2 (en) 1998-07-20 2003-02-25 Andrx Pharmaceuticals, Inc. Diltiazem controlled release formulation and method of manufacture
US6635277B2 (en) 2000-04-12 2003-10-21 Wockhardt Limited Composition for pulsatile delivery of diltiazem and process of manufacture
US6696066B2 (en) 1997-12-22 2004-02-24 Euro-Celtique S.A. Opioid agonist/antagonist combinations
US6696088B2 (en) 2000-02-08 2004-02-24 Euro-Celtique, S.A. Tamper-resistant oral opioid agonist formulations
US20040047907A1 (en) * 2000-10-30 2004-03-11 Benjamin Oshlack Controlled release hydrocodone formulations
US20040096500A1 (en) * 1991-11-27 2004-05-20 Benjamin Oshlack Controlled release oxycodone compositions
US20040170680A1 (en) * 2001-05-02 2004-09-02 Benjamin Oshlack Once-a-day oxycodone formulations
US6806294B2 (en) 1998-10-15 2004-10-19 Euro-Celtique S.A. Opioid analgesic
US20040266807A1 (en) * 1999-10-29 2004-12-30 Euro-Celtique, S.A. Controlled release hydrocodone formulations
US20060153914A1 (en) * 1999-12-10 2006-07-13 Biovail Laboratories International S.R.L. Chronotherapeutic diltiazem formulations and the administration thereof
US20060183779A1 (en) * 2002-03-07 2006-08-17 Boehringer Ingelheim Pharma Gmbh & Co., Kg Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1h-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof
US7108866B1 (en) 1999-12-10 2006-09-19 Biovall Laboratories International Srl Chronotherapeutic diltiazem formulations and the administration thereof
US20070275062A1 (en) * 1993-06-18 2007-11-29 Benjamin Oshlack Controlled release oxycodone compositions
US20080075781A1 (en) * 1992-11-25 2008-03-27 Purdue Pharma Lp Controlled release oxycodone compositions
CN100411611C (zh) * 2002-04-05 2008-08-20 欧洲凯尔蒂克公司 用于持续,不变且独立释放活性化合物的基质
US7682633B2 (en) 2006-06-19 2010-03-23 Alpharma Pharmaceuticals, Llc Pharmaceutical composition
US7740881B1 (en) 1993-07-01 2010-06-22 Purdue Pharma Lp Method of treating humans with opioid formulations having extended controlled release
US7914818B2 (en) 2001-08-06 2011-03-29 Purdue Pharma L.P. Opioid agonist formulations with releasable and sequestered antagonist
US20110104214A1 (en) * 2004-04-15 2011-05-05 Purdue Pharma L.P. Once-a-day oxycodone formulations
US7943173B2 (en) 2001-07-18 2011-05-17 Purdue Pharma L.P. Pharmaceutical combinations of oxycodone and naloxone
US8182836B2 (en) 2003-04-08 2012-05-22 Elite Laboratories, Inc. Abuse-resistant oral dosage forms and method of use thereof
ITFI20110172A1 (it) * 2011-08-08 2013-02-09 Valpharma Sa Formulazione multiparticolata a rilascio modificato di diltiazem hcl.
US8465774B2 (en) 2001-08-06 2013-06-18 Purdue Pharma L.P. Sequestered antagonist formulations
US8518925B2 (en) 2004-06-08 2013-08-27 Euro-Celtique S.A. Opioids for the treatment of the chronic obstructive pulmonary disease (COPD)
US8623418B2 (en) 2007-12-17 2014-01-07 Alpharma Pharmaceuticals Llc Pharmaceutical composition
US8685444B2 (en) 2002-09-20 2014-04-01 Alpharma Pharmaceuticals Llc Sequestering subunit and related compositions and methods
US8969369B2 (en) 2001-05-11 2015-03-03 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9149436B2 (en) 2003-04-21 2015-10-06 Purdue Pharma L.P. Pharmaceutical product comprising a sequestered agent
USRE45822E1 (en) 2001-08-06 2015-12-22 Purdue Pharma L.P. Oral dosage form comprising a therapeutic agent and an adverse-effect agent
US9271940B2 (en) 2009-03-10 2016-03-01 Purdue Pharma L.P. Immediate release pharmaceutical compositions comprising oxycodone and naloxone
US10071089B2 (en) 2013-07-23 2018-09-11 Euro-Celtique S.A. Combination of oxycodone and naloxone for use in treating pain in patients suffering from pain and a disease resulting in intestinal dysbiosis and/or increasing the risk for intestinal bacterial translocation
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
US10258235B2 (en) 2005-02-28 2019-04-16 Purdue Pharma L.P. Method and device for the assessment of bowel function

Families Citing this family (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9301220D0 (sv) * 1993-04-14 1993-04-14 Kabi Pharmacia Ab Manufacturing matrices
US5914134A (en) * 1997-01-27 1999-06-22 Wockhardt Europe Limited Process for the pulsatile delivery of diltiazem HCL and product produced thereby
US7060734B1 (en) 1997-09-09 2006-06-13 Alza Corporation Pharmaceutical coating composition and method of use
JP2001515855A (ja) * 1997-09-09 2001-09-25 アルザ・コーポレーション 薬剤コーティング組成物と使用方法
US5891845A (en) * 1997-11-21 1999-04-06 Fuisz Technologies Ltd. Drug delivery systems utilizing liquid crystal structures
EP1041988A4 (en) * 1997-12-22 2002-03-13 Euro Celtique Sa METHOD FOR PREVENTING ABUSE OF OPIOID DOSES FORMS
US6432448B1 (en) 1999-02-08 2002-08-13 Fmc Corporation Edible coating composition
US6723342B1 (en) 1999-02-08 2004-04-20 Fmc Corporation Edible coating composition
US6410255B1 (en) * 1999-05-05 2002-06-25 Aurora Biosciences Corporation Optical probes and assays
NZ515675A (en) 1999-05-14 2004-06-25 Nereus Pharmaceuticals Inc Novel interleukin-1 and tumor necrosis factor-alpha modulators, syntheses of said modulators and methods of using said modulators
GB9913979D0 (en) 1999-06-17 1999-08-18 Univ Wales Medicine Spheroid preparation
US6500462B1 (en) 1999-10-29 2002-12-31 Fmc Corporation Edible MCC/PGA coating composition
CA2400642A1 (en) * 2000-02-23 2001-08-30 Vertex Pharmaceuticals (San Diego) Llc Modified fluorescent proteins
US6852031B1 (en) * 2000-11-22 2005-02-08 Igt EZ pay smart card and tickets system
GB0025208D0 (en) * 2000-10-13 2000-11-29 Euro Celtique Sa Delayed release pharmaceutical formulations
AU4322802A (en) * 2000-11-16 2002-06-24 Univ California Marine actinomycete taxon for drug and fermentation product dicovery
TR200300731T2 (tr) 2000-11-28 2004-08-23 Fmc Corporation Yenebilir PGA kaplama bileşimi
US7176232B2 (en) 2002-06-24 2007-02-13 The Regents Of The University Of California Salinosporamides and methods for use thereof
AU2003296908A1 (en) * 2002-09-27 2004-05-04 Nereus Pharmaceuticals, Inc. Macrocyclic lactams
US20040208932A1 (en) * 2003-04-17 2004-10-21 Ramachandran Thembalath Stabilized paroxetine hydrochloride formulation
NZ544588A (en) * 2003-06-20 2010-06-25 Nereus Pharmaceuticals Inc Use of salinosporamide A and analogs thereof for the treatment of cancer, inflammation and infectious diseases
ZA200600473B (en) * 2003-06-20 2007-04-25 Univ California Salinosporamides and methods for use thereof
CA2445420A1 (en) * 2003-07-29 2005-01-29 Invitrogen Corporation Kinase and phosphatase assays
US7727752B2 (en) * 2003-07-29 2010-06-01 Life Technologies Corporation Kinase and phosphatase assays
US7619059B2 (en) * 2003-07-29 2009-11-17 Life Technologies Corporation Bimolecular optical probes
CA2538797A1 (en) * 2003-09-12 2005-03-24 Invitrogen Corporation Multiplex binding and activity assays
EP1711486B1 (en) * 2004-01-23 2011-05-11 Nereus Pharmaceuticals, Inc. Bis-indole pyrroles useful as antimicrobial agents
EP1812443A2 (en) 2004-04-30 2007-08-01 Nereus Pharmaceuticals, Inc. [3.2.0] heterocyclic compounds and methods of using the same
US7579371B2 (en) 2004-04-30 2009-08-25 Nereus Pharmaceuticals, Inc. Methods of using [3.2.0] heterocyclic compounds and analogs thereof
US7619007B2 (en) 2004-11-23 2009-11-17 Adamas Pharmaceuticals, Inc. Method and composition for administering an NMDA receptor antagonist to a subject
WO2006058059A2 (en) 2004-11-23 2006-06-01 Neuromolecular Pharmaceuticals, Inc. Composition comprising a sustained release coating or matrix and an nmda receptor antagonist, method for administration such nmda antagonist to a subject
EP1845968A2 (en) 2004-11-24 2007-10-24 Neuromolecular Pharmaceuticals, Inc Composition comprising an nmda receptor antagonist and levodopa and use thereof for treating neurological disease
US20070225350A1 (en) * 2004-12-03 2007-09-27 Anderson Kenneth C Compositions and methods for treating neoplastic diseases
AU2006228535A1 (en) * 2005-03-31 2006-10-05 Rafael Armament Development Authority Ltd. Apparatus for treating particles and liquids by ultrasound
MX2007012374A (es) 2005-04-06 2008-02-22 Adamas Pharmaceuticals Inc Metodos y composiciones para el tratamiento de condiciones relacionadas con cns.
WO2007015757A2 (en) 2005-07-21 2007-02-08 Nereus Pharmaceuticals, Inc. Interleukin-1 and tumor necrosis factor-a modulators; syntheses of such modulators and methods of using such modulators
CA2671200A1 (en) * 2006-07-21 2008-01-24 Lab International Srl Hydrophilic abuse deterrent delivery system
EP1920767A1 (en) * 2006-11-09 2008-05-14 Abbott GmbH & Co. KG Melt-processed imatinib dosage form
WO2008095195A2 (en) * 2007-02-02 2008-08-07 Nereus Pharmaceuticals, Inc. Lyophilized formulations of salinosporamide a
US20090017167A1 (en) * 2007-07-11 2009-01-15 Herbalife International Inc. Mixture and beverage made therefrom for protecting cellular hydration
US8394816B2 (en) * 2007-12-07 2013-03-12 Irene Ghobrial Methods of using [3.2.0] heterocyclic compounds and analogs thereof in treating Waldenstrom's Macroglobulinemia
WO2009088673A2 (en) * 2007-12-17 2009-07-16 Alpharma Pharmaceuticals, Llc Pharmaceutical composition
US20100151014A1 (en) * 2008-12-16 2010-06-17 Alpharma Pharmaceuticals, Llc Pharmaceutical composition
EP2219612A4 (en) * 2007-12-17 2013-10-30 Paladin Labs Inc CONTROLLED RELEASE FORMULATION AVOIDING IMPROPER USES
MX2010012341A (es) * 2008-05-12 2010-12-06 Nereus Pharmaceuticals Inc Derivados de salinosporamida como inhibidores de proteasoma.
CN105456267A (zh) * 2008-07-07 2016-04-06 欧洲凯尔特公司 阿片类拮抗剂治疗尿潴留的用途
CA2782556C (en) 2009-12-02 2018-03-27 Adamas Pharmaceuticals, Inc. Amantadine compositions and methods of use
US10463611B2 (en) 2011-06-08 2019-11-05 Sti Pharma, Llc Controlled absorption water-soluble pharmaceutically active organic compound formulation for once-daily administration
US10154971B2 (en) 2013-06-17 2018-12-18 Adamas Pharma, Llc Methods of administering amantadine
MX2017002750A (es) 2014-09-02 2017-08-02 Singh Bhupinder Metodo para marcar una molecula deuterada o no deuterada y formulaciones farmaceuticas para tratamiento.
IL251588B2 (en) 2014-10-08 2024-09-01 Pacific Northwest Res Institute Methods and preparations for increasing the potency of antifungal agents
EP3397253A1 (en) 2015-12-30 2018-11-07 Adamas Pharmaceuticals, Inc. Methods and compositions for the treatment of seizure-related disorders
WO2018200885A1 (en) 2017-04-26 2018-11-01 Neurocentria, Inc. Magnesium compositions and methods of use
CN112533614A (zh) 2018-03-28 2021-03-19 美国康宝莱国际公司 多糖的乙酰化

Citations (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0106443A2 (en) * 1982-08-13 1984-04-25 Benzon Pharma A/S Pharmaceutical oral-controlled release multiple-units formulation
US4456628A (en) * 1981-01-07 1984-06-26 Bauer Kurt H Process for film-coating a particulate solid, and emulsions for conducting the process
EP0149920A2 (en) * 1983-12-22 1985-07-31 ELAN CORPORATION, Plc Pharmaceutical formulation
EP0154009A1 (en) * 1983-12-09 1985-09-11 Euro-Celtique S.A. Use of a thiazide diuretic for the manufacture of a non-diuretic antihypertensive medicament
EP0163000A2 (de) * 1984-02-01 1985-12-04 3 M Medica GmbH Pharmazeutisches Produkt in Form von Pellets mit kontinuierlicher, verzögerter Wirkstoffabgabe
GB2179251A (en) * 1985-08-16 1987-03-04 Alza Corp Osmotic dispenser system
EP0220670A2 (en) * 1985-10-23 1987-05-06 Eisai Co., Ltd. Multilayer granule
WO1988002253A1 (en) * 1986-09-30 1988-04-07 Roberto Valducci Coating membrane and compositions prepared therefrom
EP0288732A2 (en) * 1987-04-28 1988-11-02 E.R. Squibb & Sons, Inc. New pharmaceutical compositions in the form of beadlets and method
US4808413A (en) * 1987-04-28 1989-02-28 E. R. Squibb & Sons, Inc. Pharmaceutical compositions in the form of beadlets and method
EP0315414A1 (en) * 1987-11-06 1989-05-10 Tanabe Seiyaku Co., Ltd. Controlled release dosage form
GB2209280A (en) * 1987-09-03 1989-05-10 Alza Corp Osmotic drug dispenser
EP0317855A2 (de) * 1987-11-24 1989-05-31 Beiersdorf Aktiengesellschaft Pharmazeutische Präparate
EP0320097A1 (en) * 1987-10-16 1989-06-14 ELAN CORPORATION, Plc Controlled absorption diltiazem formulations
EP0322277A1 (fr) * 1987-12-21 1989-06-28 Synthelabo Formulation pharmaceutique à libération prolongée
EP0327086A2 (en) * 1988-02-03 1989-08-09 Eisai Co., Ltd. Multi-layer granule
WO1989008448A1 (en) * 1988-03-10 1989-09-21 Nycomed As Enteric coated spheroidal granules
AU3227389A (en) * 1988-03-31 1989-10-05 Tanabe Seiyaku Co., Ltd. Controlled release pharmaceutical preparation and method for producing the same
EP0340105A1 (fr) * 1988-04-27 1989-11-02 Sanofi Microbilles de diltiazem, leur procédé de fabrication et compositions pharmaceutiques à libération prolongée les contenant
US4894240A (en) * 1983-12-22 1990-01-16 Elan Corporation Plc Controlled absorption diltiazem formulation for once-daily administration
US4917899A (en) * 1983-12-22 1990-04-17 Elan Corporation Plc Controlled absorption diltiazem formulation
US4917900A (en) * 1987-03-27 1990-04-17 Burroughs Wellcome Co. Controlled release formulations containing zidovudine
EP0373417A1 (en) * 1988-11-30 1990-06-20 Schering Corporation Sustained release diltiazem formulation
GB2227172A (en) * 1989-01-23 1990-07-25 Ciba Geigy Ag Low dose benazepril/thiazide diuretic composition
US4960596A (en) * 1987-11-26 1990-10-02 Ethypharm Slow-release preparation of diltiazem, and a medicine provided thereby
WO1991001722A1 (en) * 1989-08-09 1991-02-21 Lejus Medical Aktiebolag Diltiazem containing pharmaceutical compositions
US5002776A (en) * 1983-12-22 1991-03-26 Elan Corporation, Plc Controlled absorption diltiazem formulations
AU6798890A (en) * 1989-12-28 1991-07-04 Rohm Gmbh & Co. Kg Controlled release pharmaceutical preparation and method for producing the same
EP0446753A1 (en) * 1990-03-06 1991-09-18 Vectorpharma International S.P.A. Therapeutic compositions with controlled release of medicaments supported on crosslinked polymers and coated with polymer films and their preparation process
EP0514814A1 (en) * 1991-05-20 1992-11-25 Hoechst Marion Roussel, Inc. Diltiazem formulation
US5219621A (en) * 1987-10-16 1993-06-15 Elan Corporation, Plc Methods of treatment with diltiazem formulations
US5286497A (en) * 1991-05-20 1994-02-15 Carderm Capital L.P. Diltiazem formulation
US5364620A (en) * 1983-12-22 1994-11-15 Elan Corporation, Plc Controlled absorption diltiazem formulation for once daily administration

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3709188A1 (de) * 1987-03-20 1988-09-29 Mannesmann Ag Ausgiessrohr fuer metallurgische gefaesse
BE1000794A4 (nl) * 1987-07-30 1989-04-04 Schelde Delta Bv Met Beperkte Werkwijze voor het bij chemische processen immobiliseren van komponenten in een fluidumstroom, en inrichtingen die deze werkwijze toepassen.

Patent Citations (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4456628A (en) * 1981-01-07 1984-06-26 Bauer Kurt H Process for film-coating a particulate solid, and emulsions for conducting the process
EP0106443A2 (en) * 1982-08-13 1984-04-25 Benzon Pharma A/S Pharmaceutical oral-controlled release multiple-units formulation
EP0154009A1 (en) * 1983-12-09 1985-09-11 Euro-Celtique S.A. Use of a thiazide diuretic for the manufacture of a non-diuretic antihypertensive medicament
EP0149920A2 (en) * 1983-12-22 1985-07-31 ELAN CORPORATION, Plc Pharmaceutical formulation
US5002776A (en) * 1983-12-22 1991-03-26 Elan Corporation, Plc Controlled absorption diltiazem formulations
CH662507A5 (fr) * 1983-12-22 1987-10-15 Elan Corp Plc Composition pour l'administration par la voie orale de la diltiazem.
US4721619A (en) * 1983-12-22 1988-01-26 Elan Corporation P.L.C. Controlled absorption diltiazen pharmaceutical formulation
US4917899A (en) * 1983-12-22 1990-04-17 Elan Corporation Plc Controlled absorption diltiazem formulation
US4894240A (en) * 1983-12-22 1990-01-16 Elan Corporation Plc Controlled absorption diltiazem formulation for once-daily administration
US5364620A (en) * 1983-12-22 1994-11-15 Elan Corporation, Plc Controlled absorption diltiazem formulation for once daily administration
EP0163000A2 (de) * 1984-02-01 1985-12-04 3 M Medica GmbH Pharmazeutisches Produkt in Form von Pellets mit kontinuierlicher, verzögerter Wirkstoffabgabe
GB2179251A (en) * 1985-08-16 1987-03-04 Alza Corp Osmotic dispenser system
EP0220670A2 (en) * 1985-10-23 1987-05-06 Eisai Co., Ltd. Multilayer granule
WO1988002253A1 (en) * 1986-09-30 1988-04-07 Roberto Valducci Coating membrane and compositions prepared therefrom
US4917900A (en) * 1987-03-27 1990-04-17 Burroughs Wellcome Co. Controlled release formulations containing zidovudine
US4808413A (en) * 1987-04-28 1989-02-28 E. R. Squibb & Sons, Inc. Pharmaceutical compositions in the form of beadlets and method
EP0288732A2 (en) * 1987-04-28 1988-11-02 E.R. Squibb & Sons, Inc. New pharmaceutical compositions in the form of beadlets and method
US4808413B1 (no) * 1987-04-28 1991-09-10 Squibb & Sons Inc
GB2209280A (en) * 1987-09-03 1989-05-10 Alza Corp Osmotic drug dispenser
US5219621A (en) * 1987-10-16 1993-06-15 Elan Corporation, Plc Methods of treatment with diltiazem formulations
EP0320097A1 (en) * 1987-10-16 1989-06-14 ELAN CORPORATION, Plc Controlled absorption diltiazem formulations
EP0315414A1 (en) * 1987-11-06 1989-05-10 Tanabe Seiyaku Co., Ltd. Controlled release dosage form
EP0317855A2 (de) * 1987-11-24 1989-05-31 Beiersdorf Aktiengesellschaft Pharmazeutische Präparate
US4960596A (en) * 1987-11-26 1990-10-02 Ethypharm Slow-release preparation of diltiazem, and a medicine provided thereby
EP0322277A1 (fr) * 1987-12-21 1989-06-28 Synthelabo Formulation pharmaceutique à libération prolongée
US5112621A (en) * 1987-12-21 1992-05-12 Synthelabo Sustained release pharmaceutical composition of diltiazem
EP0327086A2 (en) * 1988-02-03 1989-08-09 Eisai Co., Ltd. Multi-layer granule
WO1989008448A1 (en) * 1988-03-10 1989-09-21 Nycomed As Enteric coated spheroidal granules
AU3227389A (en) * 1988-03-31 1989-10-05 Tanabe Seiyaku Co., Ltd. Controlled release pharmaceutical preparation and method for producing the same
EP0340105A1 (fr) * 1988-04-27 1989-11-02 Sanofi Microbilles de diltiazem, leur procédé de fabrication et compositions pharmaceutiques à libération prolongée les contenant
EP0373417A1 (en) * 1988-11-30 1990-06-20 Schering Corporation Sustained release diltiazem formulation
GB2227172A (en) * 1989-01-23 1990-07-25 Ciba Geigy Ag Low dose benazepril/thiazide diuretic composition
WO1991001722A1 (en) * 1989-08-09 1991-02-21 Lejus Medical Aktiebolag Diltiazem containing pharmaceutical compositions
AU6798890A (en) * 1989-12-28 1991-07-04 Rohm Gmbh & Co. Kg Controlled release pharmaceutical preparation and method for producing the same
EP0446753A1 (en) * 1990-03-06 1991-09-18 Vectorpharma International S.P.A. Therapeutic compositions with controlled release of medicaments supported on crosslinked polymers and coated with polymer films and their preparation process
EP0514814A1 (en) * 1991-05-20 1992-11-25 Hoechst Marion Roussel, Inc. Diltiazem formulation
US5286497A (en) * 1991-05-20 1994-02-15 Carderm Capital L.P. Diltiazem formulation

Non-Patent Citations (16)

* Cited by examiner, † Cited by third party
Title
(Abstract) No. 1593062, "Pharmaceutical controlled release compositions", 16 Sep. 1977, Richter Gedeon Vegyeszeti Gyar RT.
(Abstract) No. 1593062, Pharmaceutical controlled release compositions , 16 Sep. 1977, Richter Gedeon Vegyeszeti Gyar RT. *
(Abstract) No. 22342C/13 (EP 9 657), Diuretic compositions containing potassium retaining agents comprising 2,4 di:amino 5 aminobenzl pyrimidine derivatives , Hoffman LaRoche AG. *
(Abstract) No. 22342C/13 (EP-9-657), "Diuretic compositions containing potassium retaining agents -comprising 2,4-di:amino-5-aminobenzl-pyrimidine derivatives", Hoffman-LaRoche AG.
(Abstract) Pharmaceuticals, p. 3, Week 8407, Abstract #84-038350/07 (EP-100-061-A), "Pharmaceutical dosage units with enhanced bio:availability -especially hydro:chloro:thiazide-triameterene mixtures for uniform absoprtion", Mylan Pharm, Inc.
(Abstract) Pharmaceuticals, p. 3, Week 8407, Abstract 84 038350/07 (EP 100 061 A), Pharmaceutical dosage units with enhanced bio:availability especially hydro:chloro:thiazide triameterene mixtures for uniform absoprtion , Mylan Pharm, Inc. *
(Abstract) Pharmaceuticals, p. 6, Week 8528, Abstract #85-166500/28 (EP-147-780-A), "Pharmaceutical composition for oral, rectal or vaginal administration -with polvinyl alcohol film coating for controlled and prolonged release", (Merck & Co., Inc.
(Abstract) Pharmaceuticals, p. 6, Week 8528, Abstract 85 166500/28 (EP 147 780 A), Pharmaceutical composition for oral, rectal or vaginal administration with polvinyl alcohol film coating for controlled and prolonged release , (Merck & Co., Inc. *
(Abstract) Pharmaceuticals, Week K25, Abstract #59112 K/25 (EP-81-006), "Composition of beta-adrenergic blocer and tetra-hydro-benzazepine -useful as atihypertensive and in improving efficiency of kidney function", Alcide Co. Ltd. Partn (ALLI).
(Abstract) Pharmaceuticals, Week K25, Abstract 59112 K/25 (EP 81 006), Composition of beta adrenergic blocer and tetra hydro benzazepine useful as atihypertensive and in improving efficiency of kidney function , Alcide Co. Ltd. Partn (ALLI). *
(Abstract), No. 85 184021/31 (EP 154 009 A), Treatment of hypertension in patent by administration of thiazide diuretic at level to cause antihypetensive action with diuresia , Euro Celtique, S.A. *
(Abstract), No. 85-184021/31 (EP-154-009-A), "Treatment of hypertension in patent -by administration of thiazide diuretic at level to cause antihypetensive action with diuresia", Euro-Celtique, S.A.
(Abstract), No. 89 158961/22 (EP 317 855 A), Combination of moxonidine, hydro:chloro:thiazide and opt. triamteren for long term treatment of hypertonia and oedemas , Beiersdorf AG. *
(Abstract), No. 89-158961/22 (EP-317-855-A), "Combination of moxonidine, hydro:chloro:thiazide and opt. triamteren -for long-term treatment of hypertonia and oedemas", Beiersdorf AG.
(Abstract), Pharmaceuticals, p. 8, Week K23, Abstract #54403 K/23 (EP-80-341), "Pharmaceutical multiple units formulation -with enterically coated cores for reduced peak plasma drug concentration", Benzon A AS.
(Abstract), Pharmaceuticals, p. 8, Week K23, Abstract 54403 K/23 (EP 80 341), Pharmaceutical multiple units formulation with enterically coated cores for reduced peak plasma drug concentration , Benzon A AS. *

Cited By (141)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060057210A1 (en) * 1991-11-27 2006-03-16 Purdue Pharma L.P. Controlled release oxycodone compositions
US20040185098A1 (en) * 1991-11-27 2004-09-23 Benjamin Oshlack Controlled release oxycodone compositions
US20040096500A1 (en) * 1991-11-27 2004-05-20 Benjamin Oshlack Controlled release oxycodone compositions
US6905709B2 (en) 1991-12-24 2005-06-14 Purdue Pharma, Lp Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US6129933A (en) * 1991-12-24 2000-10-10 Purdue Pharma Lp Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US6316031B1 (en) * 1991-12-24 2001-11-13 Purdue Pharma Lp Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US20040228917A1 (en) * 1991-12-24 2004-11-18 Purdue Pharma Lp Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US7316821B2 (en) 1991-12-24 2008-01-08 Purdue Pharma, L.P. Stabilized controlled release substrate having a coating derived from an aqueous dispersion of hydrophobic polymer
US20080075781A1 (en) * 1992-11-25 2008-03-27 Purdue Pharma Lp Controlled release oxycodone compositions
US20100092570A1 (en) * 1992-11-25 2010-04-15 Purdue Pharma L.P. Controlled release oxycodone compositions
US6013284A (en) * 1993-03-02 2000-01-11 Biovector Therapeutics S.A. Synthetic particulate vectors and preparation process
US20070275062A1 (en) * 1993-06-18 2007-11-29 Benjamin Oshlack Controlled release oxycodone compositions
US20100034876A1 (en) * 1993-06-18 2010-02-11 Purdue Pharma L.P. Controlled release oxycodone compositions
US7740881B1 (en) 1993-07-01 2010-06-22 Purdue Pharma Lp Method of treating humans with opioid formulations having extended controlled release
US6143322A (en) * 1993-07-01 2000-11-07 Purdue Pharma L.P. Method of treating humans with opioid formulations having extended controlled release
US6103261A (en) * 1993-07-01 2000-08-15 Purdue Pharma Lp Opioid formulations having extended controlled release
US6033687A (en) * 1995-01-05 2000-03-07 F.H. Faulding & Co. Controlled absorption diltiazem pharmaceutical formulation
US6214385B1 (en) 1995-01-05 2001-04-10 Grant W. Heinicke Controlled absorption diltiazem pharmaceutical formulation
US6399096B1 (en) 1995-09-22 2002-06-04 Euro-Celtique S.A. Pharmaceutical formulation
US8506998B2 (en) 1995-09-22 2013-08-13 Euro-Celtique S.A. Pharmaceutical formulation
US7749542B2 (en) 1997-12-22 2010-07-06 Purdue Pharma Lp Opioid agonist/antagonist combinations
US8932630B1 (en) 1997-12-22 2015-01-13 Purdue Pharma L.P Opioid agonist/antagonist combinations
US6696066B2 (en) 1997-12-22 2004-02-24 Euro-Celtique S.A. Opioid agonist/antagonist combinations
US8673355B2 (en) 1997-12-22 2014-03-18 Purdue Pharma L.P. Opioid agonist/antagonist combinations
US9205082B2 (en) 1997-12-22 2015-12-08 Purdue Pharma L.P. Opioid agonist/antagonist combinations
US8105631B2 (en) 1997-12-22 2012-01-31 Purdue Pharma L.P. Opioid agonist/antagonist combinations
US6524620B2 (en) 1998-07-20 2003-02-25 Andrx Pharmaceuticals, Inc. Diltiazem controlled release formulation and method of manufacture
US6806294B2 (en) 1998-10-15 2004-10-19 Euro-Celtique S.A. Opioid analgesic
US9675611B1 (en) 1999-10-29 2017-06-13 Purdue Pharma L.P. Methods of providing analgesia
US10179130B2 (en) 1999-10-29 2019-01-15 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9669022B2 (en) 1999-10-29 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
US8975273B2 (en) 1999-10-29 2015-03-10 Purdue Pharma L.P. Controlled release hydrocodone formulations
US8980291B2 (en) 1999-10-29 2015-03-17 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9669024B2 (en) 1999-10-29 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9056107B1 (en) 1999-10-29 2015-06-16 Purdue Pharma L.P. Controlled release hydrocodone formulations
US7943174B2 (en) 1999-10-29 2011-05-17 Purdue Pharma L.P. Controlled release hydrocodone formulations
US10076516B2 (en) 1999-10-29 2018-09-18 Purdue Pharma L.P. Methods of manufacturing oral dosage forms
US9278074B2 (en) 1999-10-29 2016-03-08 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9320717B2 (en) 1999-10-29 2016-04-26 Purdue Pharma L.P. Controlled release hydrocodone formulations
US20040266807A1 (en) * 1999-10-29 2004-12-30 Euro-Celtique, S.A. Controlled release hydrocodone formulations
US20060153914A1 (en) * 1999-12-10 2006-07-13 Biovail Laboratories International S.R.L. Chronotherapeutic diltiazem formulations and the administration thereof
US7108866B1 (en) 1999-12-10 2006-09-19 Biovall Laboratories International Srl Chronotherapeutic diltiazem formulations and the administration thereof
US10588865B2 (en) 2000-02-08 2020-03-17 Purdue Pharma L.P. Tamper resistant oral opioid agonist formulations
US9456989B2 (en) 2000-02-08 2016-10-04 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US9278073B2 (en) 2000-02-08 2016-03-08 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US7718192B2 (en) 2000-02-08 2010-05-18 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US7682632B2 (en) 2000-02-08 2010-03-23 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US10350173B2 (en) 2000-02-08 2019-07-16 Purdue Pharma L.P. Tamper resistant oral opioid agonist formulations
US7842309B2 (en) 2000-02-08 2010-11-30 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US9801828B2 (en) 2000-02-08 2017-10-31 Purdue Pharma L.P. Tamper resistant oral opioid agonist formulations
US7842311B2 (en) 2000-02-08 2010-11-30 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US7658939B2 (en) 2000-02-08 2010-02-09 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US8936812B2 (en) 2000-02-08 2015-01-20 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US6696088B2 (en) 2000-02-08 2004-02-24 Euro-Celtique, S.A. Tamper-resistant oral opioid agonist formulations
US8236351B2 (en) 2000-02-08 2012-08-07 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
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US8586088B2 (en) 2000-02-08 2013-11-19 Purdue Pharma L.P. Tamper-resistant oral opioid agonist formulations
US6635277B2 (en) 2000-04-12 2003-10-21 Wockhardt Limited Composition for pulsatile delivery of diltiazem and process of manufacture
US9289391B2 (en) 2000-10-30 2016-03-22 Purdue Pharma L.P. Controlled release hydrocodone formulations
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US10022368B2 (en) 2000-10-30 2018-07-17 Purdue Pharma L.P. Methods of manufacturing oral formulations
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US8951555B1 (en) 2000-10-30 2015-02-10 Purdue Pharma L.P. Controlled release hydrocodone formulations
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US20090202629A1 (en) * 2000-10-30 2009-08-13 Purdue Pharma Lp Controlled release hydrocodone formulations
US9669023B2 (en) 2000-10-30 2017-06-06 Purdue Pharma L.P. Controlled release hydrocodone formulations
US9655893B2 (en) 2001-05-02 2017-05-23 Purdue Pharma L.P. Once-a-day oxycodone formulations
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US7846476B2 (en) 2001-05-02 2010-12-07 Purdue Pharma L.P. Once-a-day oxycodone formulations
US9750736B2 (en) 2001-05-02 2017-09-05 Purdue Pharma L.P. Oxycodone formulations
US20040170680A1 (en) * 2001-05-02 2004-09-02 Benjamin Oshlack Once-a-day oxycodone formulations
US9161937B2 (en) 2001-05-11 2015-10-20 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9358230B1 (en) 2001-05-11 2016-06-07 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9168252B2 (en) 2001-05-11 2015-10-27 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9511066B2 (en) 2001-05-11 2016-12-06 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9480685B2 (en) 2001-05-11 2016-11-01 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US8969369B2 (en) 2001-05-11 2015-03-03 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9345701B1 (en) 2001-05-11 2016-05-24 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9056051B2 (en) 2001-05-11 2015-06-16 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9084729B2 (en) 2001-05-11 2015-07-21 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9283216B2 (en) 2001-05-11 2016-03-15 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US9283221B2 (en) 2001-05-11 2016-03-15 Purdue Pharma L.P. Abuse-resistant controlled-release opioid dosage form
US7943173B2 (en) 2001-07-18 2011-05-17 Purdue Pharma L.P. Pharmaceutical combinations of oxycodone and naloxone
US7914818B2 (en) 2001-08-06 2011-03-29 Purdue Pharma L.P. Opioid agonist formulations with releasable and sequestered antagonist
US9949930B2 (en) 2001-08-06 2018-04-24 Purdue Pharma L.P. Opioid agonist formulations with releasable and sequestered antagonist
USRE45822E1 (en) 2001-08-06 2015-12-22 Purdue Pharma L.P. Oral dosage form comprising a therapeutic agent and an adverse-effect agent
US8758825B2 (en) 2001-08-06 2014-06-24 Purdue Pharma L.P. Sequestered antagonist formulations
US8815287B2 (en) 2001-08-06 2014-08-26 Purdue Pharma L.P. Opiod agonist formulations with releasable and sequestered antagonist
US8518443B2 (en) 2001-08-06 2013-08-27 Purdue Pharma, L.P. Opioid agonist formulations with releasable and sequestered antagonist
US8231901B2 (en) 2001-08-06 2012-07-31 Purdue Pharma L.P. Opioid agonist formulations with releasable and sequestered antagonist
US8465774B2 (en) 2001-08-06 2013-06-18 Purdue Pharma L.P. Sequestered antagonist formulations
US20060183779A1 (en) * 2002-03-07 2006-08-17 Boehringer Ingelheim Pharma Gmbh & Co., Kg Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1h-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionic acid ethyl ester and the salts thereof
US9925174B2 (en) * 2002-03-07 2018-03-27 Boehringer Ingelheim International Gmbh Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonyl-amino-imino-methyl)-phenylamino]-methyl}-1-methyl-1 H-benzimidazol acid ethyl ester and the salts thereof
US9655855B2 (en) 2002-04-05 2017-05-23 Purdue Pharma L.P. Matrix for sustained, invariant and independent release of active compounds
US8846090B2 (en) 2002-04-05 2014-09-30 Euro-Celtique S.A. Matrix for sustained, invariant and independent release of active compounds
US9907793B2 (en) 2002-04-05 2018-03-06 Purdue Pharma L.P. Pharmaceutical preparation containing oxycodone and naloxone
US10420762B2 (en) 2002-04-05 2019-09-24 Purdue Pharma L.P. Pharmaceutical preparation containing oxycodone and naloxone
CN100411611C (zh) * 2002-04-05 2008-08-20 欧洲凯尔蒂克公司 用于持续,不变且独立释放活性化合物的基质
US9555000B2 (en) 2002-04-05 2017-01-31 Purdue Pharma L.P. Pharmaceutical preparation containing oxycodone and naloxone
US8846091B2 (en) 2002-04-05 2014-09-30 Euro-Celtique S.A. Matrix for sustained, invariant and independent release of active compounds
US8685444B2 (en) 2002-09-20 2014-04-01 Alpharma Pharmaceuticals Llc Sequestering subunit and related compositions and methods
US8685443B2 (en) 2002-09-20 2014-04-01 Alpharma Pharmaceuticals Llc Sequestering subunit and related compositions and methods
US8425933B2 (en) 2003-04-08 2013-04-23 Elite Laboratories, Inc. Abuse-resistant oral dosage forms and method of use thereof
US8182836B2 (en) 2003-04-08 2012-05-22 Elite Laboratories, Inc. Abuse-resistant oral dosage forms and method of use thereof
US8703186B2 (en) 2003-04-08 2014-04-22 Elite Laboratories, Inc. Abuse-resistant oral dosage forms and method of use thereof
US10092519B2 (en) 2003-04-21 2018-10-09 Purdue Pharma L.P. Pharmaceutical products
US9149436B2 (en) 2003-04-21 2015-10-06 Purdue Pharma L.P. Pharmaceutical product comprising a sequestered agent
US20110104214A1 (en) * 2004-04-15 2011-05-05 Purdue Pharma L.P. Once-a-day oxycodone formulations
US8518925B2 (en) 2004-06-08 2013-08-27 Euro-Celtique S.A. Opioids for the treatment of the chronic obstructive pulmonary disease (COPD)
US10258235B2 (en) 2005-02-28 2019-04-16 Purdue Pharma L.P. Method and device for the assessment of bowel function
US7682633B2 (en) 2006-06-19 2010-03-23 Alpharma Pharmaceuticals, Llc Pharmaceutical composition
US8846104B2 (en) 2006-06-19 2014-09-30 Alpharma Pharmaceuticals Llc Pharmaceutical compositions for the deterrence and/or prevention of abuse
US8877247B2 (en) 2006-06-19 2014-11-04 Alpharma Pharmaceuticals Llc Abuse-deterrent multi-layer pharmaceutical composition comprising an opioid antagonist and an opioid agonist
US8158156B2 (en) 2006-06-19 2012-04-17 Alpharma Pharmaceuticals, Llc Abuse-deterrent multi-layer pharmaceutical composition comprising an opioid antagonist and an opioid agonist
US7682634B2 (en) 2006-06-19 2010-03-23 Alpharma Pharmaceuticals, Llc Pharmaceutical compositions
US8623418B2 (en) 2007-12-17 2014-01-07 Alpharma Pharmaceuticals Llc Pharmaceutical composition
US9820983B2 (en) 2009-03-10 2017-11-21 Purdue Pharma L.P. Immediate release pharmaceutical compositions comprising oxycodone and naloxone
US9271940B2 (en) 2009-03-10 2016-03-01 Purdue Pharma L.P. Immediate release pharmaceutical compositions comprising oxycodone and naloxone
ITFI20110172A1 (it) * 2011-08-08 2013-02-09 Valpharma Sa Formulazione multiparticolata a rilascio modificato di diltiazem hcl.
EP2556826A1 (en) * 2011-08-08 2013-02-13 Valpharma S.p.A. Modified-release multiparticulate formulation of diltiazem HCL
US10071089B2 (en) 2013-07-23 2018-09-11 Euro-Celtique S.A. Combination of oxycodone and naloxone for use in treating pain in patients suffering from pain and a disease resulting in intestinal dysbiosis and/or increasing the risk for intestinal bacterial translocation

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CA2075356A1 (en) 1993-02-13
FI923582A0 (fi) 1992-08-11
JPH05201867A (ja) 1993-08-10
CN1069408A (zh) 1993-03-03
JP3019235B2 (ja) 2000-03-13
NO304406B1 (no) 1998-12-14
ATE165513T1 (de) 1998-05-15
AU2088092A (en) 1993-02-18
ES2115643T3 (es) 1998-07-01
EP0527637B1 (en) 1998-04-29
IL102778A (en) 1999-05-09
NO923128D0 (no) 1992-08-11
US5601845A (en) 1997-02-11
NO923128L (no) 1993-02-15
FI923582A (fi) 1993-02-13
IL102778A0 (en) 1993-01-31
DE69225278D1 (de) 1998-06-04
EP0527637A1 (en) 1993-02-17
CN1052398C (zh) 2000-05-17
KR930003906A (ko) 1993-03-22
AU651715B2 (en) 1994-07-28
KR100221695B1 (ko) 1999-09-15
PH31288A (en) 1998-07-06

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